Epidermal growth factor (EGF) is a 6.2 kDa polypeptide that specifically binds to the epidermal growth factor receptor (EGFR). EGF contains 53 amino acids with three internal disulfide bridges. Binding of EGF to its receptor induces a conformational change and receptor aggregation (Greenfield, et al., EMBO J. 8:4115-4123, 1989; Yarden and Schlessinger, Biochem. 26:1443-1451, 1987). Receptor aggregation stimulates an intrinsic tyrosine kinase activity in the cytoplasmic domain of EGFR, which in turn leads to recruitment and phosphorylation of other substrates, resulting in mitogenic signaling and/or a variety of other cellular activities (Pawson and Schlessinger, Curr. Biol. 3:434-442, 1994; Alroy and Yarden, FEBS Lett. 410:83-86, 1997; Riese and Stern, Bioessays 20:41-48, 1998).
The EGFR is a target for therapeutic intervention for a diverse range of conditions. Overexpression of the EGFR is associated with many types of malignancies and often correlates with poor patient prognosis. Modulating EGFR activity has influenced clinical results in the treatment of cancers (Mendelsohn and Baselga, Oncogene 19:6550-6565, 2000). Stimulation of EGFR with EGF has also been shown to accelerate wound healing, (e.g., in gastric and oral ulcers, diabetic foot ulcers, skin grafts, corneal epithelial wounds, and tympanic membrane perforations (Milani and Calabro, Microsc. Res. Tech. 53:360-371, 2001; Fujisawa, et al., J. Oral Pathol. Med. 32:358-366, 2003; Bennett, et al., Br J Surg. 90:133-146, 2003; Brown, et al., N. Engl. J. Med. 321:76-79, 1989; Lu, et al., Exp. Biol. Med. (Maywood) 226:653-664, 2001; Ma, et al., Acta Otolaryngol. 122:586-599, 2002). EGF may also regulate nerve regeneration and atherogenesis (Xian and Zhou, Mol. Neurobiol. 20:157-183, 1999; Lamb, et al., Atherosclerosis 168:191-194, 2003).